Microchimerism, dendritic cell progenitors and transplantation tolerance

Stem Cells
A W ThomsonT E Starzl

Abstract

The recent discovery of multilineage donor leukocyte microchimerism in allograft recipients up to three decades after organ transplantation implies the migration and survival of donor stem cells within the host. It has been postulated that in chimeric graft recipients, reciprocal modulation of immune responsiveness between donor and recipient leukocytes may lead, eventually, to the induction of mutual immunologic nonreactivity (tolerance). A prominent donor leukocyte, both in human organ transplant recipients and in animals, has invariably been the bone marrow-derived dendritic cell (DC). These cells have been classically perceived as the most potent antigen-presenting cells but evidence also exists for their tolerogenicity. The liver, despite its comparatively heavy leukocyte content, is the whole organ that is most capable of inducing tolerance. We have observed that DC progenitors propagated from normal mouse liver in response to GM-CSF express only low levels of major histocompatibility complex (MHC) class II antigen and little or no cell surface B7 family T cell costimulatory molecules. They fail to activate resting naive allogeneic T cells. When injected into normal allogeneic recipients, these DC progenitors migrate to T...Continue Reading

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Citations

Jul 1, 2011·Immunologic Research·Angus W ThomsonDonna Beer-Stolz
Nov 20, 1997·Transplantation Proceedings·J J Fung
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